This P60 application is the competing renewal application for the multi-site Multi-disciplinary Alcoholism Research Center (MARC). The broad focus of our research is the multi-level investigation (from lifetime diagnostic to real-time ecological) of the etiology and course of alcohol use disorders and associated comorbidity in community (rather than clinically ascertained) samples, with a particular focus on the period of young adulthood. The MARC is organized as: (1) an Administrative Core, which is responsible for coordinating MARC-based research projects with each other, and with our broader R01-supported portfolio of genetic, prospective high-risk and human experimental and ecological studies, (2) a Science Resource Core for support of (i) sample ascertainment and tracking, (ii) data-base management for our phenotypic, genotypic and environmental exposure data, and (iii) assessment coordination, (3) a Pilot Project core to facilitate the development of junior faculty as new investigators; (4) an Outreach Core, which extends our outreach through a new 2-week annual Alcohol Research Training Summer School, targeting undergraduates, to increase, nationally, the diversity of the pool of future alcoholism researchers; (5) four research projects. New Project 8 proposes 3 alcohol challenge experiments to characterize acute alcohol effects on executive cognitive functioning on the ascending versus descending limbs of the BAG curve. New Project 7 proposes a new wave of data collection for our OZ-ALC GWAS sample of N=3600, 50% with alcohol dependence history, derived from studies of the Australian Twin Panel, to update information about drinking patterns and ADD, and retrospective data about early childhood exposures (especially maltreatment). Project 6 extends our real-time Ecological Momentary Assessment study of the relationships between negative and positive affect, initiation of drinking episodes, and positive and negative reinforcement by alcohol, by focusing on a patient group characterized by severe affective dysregulation and impulsivity (Borderline Personality Disorder), who are known to have high risk of alcohol dependence. Project 5 adds a molecular epidemiology component to the prospective ABCHS cohort studies, R01-funded projects led by Anokhin, Bucholz, Chassin, Heath and Sher, to inform in prospective samples genetic associations, and GxE effects, identified in Project 7 and in other ongoing GWAS and gene-mapping studies.